CD22ΔE12 as a molecular target for RNAi therapy.
Br J Haematol
; 169(3): 401-14, 2015 May.
Article
en En
| MEDLINE
| ID: mdl-25659406
ABSTRACT
B-precursor acute lymphoblastic leukaemia (BPL) is the most common form of cancer in children and adolescents. Our recent studies have demonstrated that CD22ΔE12 is a characteristic genetic defect of therapy-refractory clones in paediatric BPL and implicated the CD22ΔE12 genetic defect in the aggressive biology of relapsed or therapy-refractory paediatric BPL. The purpose of the present study is to evaluate the biological significance of the CD22ΔE12 molecular lesion in BPL and determine if it could serve as a molecular target for RNA interference (RNAi) therapy. Here we report a previously unrecognized causal link between CD22ΔE12 and aggressive biology of human BPL cells by demonstrating that siRNA-mediated knockdown of CD22ΔE12 in primary leukaemic B-cell precursors is associated with a marked inhibition of their clonogenicity. Additionally, we report a nanoscale liposomal formulation of CD22ΔE12-specific siRNA with potent in vitro and in vivo anti-leukaemic activity against primary human BPL cells as a first-in-class RNAi therapeutic candidate targeting CD22ΔE12.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
ARN Interferente Pequeño
/
Interferencia de ARN
/
Lectina 2 Similar a Ig de Unión al Ácido Siálico
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Br J Haematol
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos